Background: The metabolism of normal prostate relies on glycolysis, with prostate cancer having reduced glycolysis and increased aerobic metabolism. Advanced glycation end products (AGEs) accumulate in tissues as a result of age and glycolytic rate. Differential AGE levels were recently observed in prostate cancer tissues.
View Article and Find Full Text PDFBackground: Many studies have addressed effects of dietary supplementation with soy protein, but most have been inconsistent and few have been long-term studies in men.
Objectives: This study was a secondary analysis of body weight, blood pressure, thyroid hormones, iron status, and clinical chemistry in a 2-y trial of soy protein supplementation in middle-aged to older men.
Methods: Data were analyzed as secondary outcomes of a randomized controlled trial of dietary supplementation with 20 g/d soy protein isolate, providing 41 mg/d total isoflavones and 23 mg/d genistein, in 44- to 75-y-old men who were at risk of cancer recurrence following prostatectomy randomized to soy (n = 50) or a casein-based placebo (n = 43).
Background: Fibrostenosis, the most serious eosinophilic esophagitis (EoE) complication, is mediated by epithelial-mesenchymal transition (EMT). Transitioned cells contribute to pathogenesis by overproducing extracellular matrix.
Objective: Our aim was to determine whether RPC4046 (anti‒IL-13 mAb) modulates EMT biomarkers in biopsy samples from adults with active EoE in a substudy of a double-blind, placebo-controlled phase 2 trial.
Multispectral fluorescence imaging on formalin-fixed paraffin-embedded (FFPE) tissues enables the detection of multiple markers in a single tissue sample that can provide information about antigen coexpression and spatial distribution of the markers. However, a lack of suitable antibodies for formalin-fixed tissues may restrict the nature of markers that can be detected. In addition, the staining method is time-consuming.
View Article and Find Full Text PDFMultiple aspects of cornea development, including the innervation of the cornea by trigeminal axons, are sensitive to embryonic levels of thyroid hormone (TH). Although previous work showed that increased TH levels could enhance the rate of axonal extension within the cornea in a thyroxine (T4)-dependent manner, details underlying the stimulatory effect of TH on cornea innervation are unclear. Here, by examining the effects throughout all stages of cornea innervation of the two main THs, triiodothyronine (T3) and T4, we provide a more complete characterization of the stimulatory effects of TH on corneal nerves and begin to unravel the underlying molecular mechanisms.
View Article and Find Full Text PDFObjective: To determine whether a computer vision-based approach applied to haematoxylin and eosin (H&E) prostate biopsy images can distinguish dutasteride-treated tissue from placebo, and identify features associated with degree of responsiveness to 5α-reductase inhibitor (5ARI) therapy.
Subjects And Methods: Our study population comprised 100 treatment-adherent men without prostate cancer assigned to dutasteride or placebo in the REDUCE trial, who had slides available from mandatory year-4 biopsies. Half of the men also provided slides from a year-2 biopsy.
Purpose: Mutations in BRCA1 are associated with familial as well as sporadic aggressive subtypes of breast cancer, but less is known about whether BRCA1 expression or subcellular localization contributes to progression in population-based settings.
Methods: We examined BRCA1 expression and subcellular localization in invasive breast cancer tissues from an ethnically diverse sample of 286 patients and 36 normal breast tissue controls. Two different methods were used to label breast cancer tissues for BRCA1: (1) Dual immunofluoresent staining with BRCA1 and cytokeratin 8/18 and (2) immunohistochemical staining using the previously validated MS110 mouse monoclonal antibody.
Context: Color normalization techniques for histology have not been empirically tested for their utility for computational pathology pipelines.
Aims: We compared two contemporary techniques for achieving a common intermediate goal - epithelial-stromal classification.
Settings And Design: Expert-annotated regions of epithelium and stroma were treated as ground truth for comparing classifiers on original and color-normalized images.
Background: Approximately 2.7 million Americans are chronically infected with hepatitis C virus (HCV). HCV patients with cirrhosis form the largest group of persons at high risk for hepatocellular carcinoma (HCC).
View Article and Find Full Text PDFA diverse body of evidence suggests that lycopene might inhibit prostate cancer development. We conducted a 6-mo repeat biopsy randomized trial among men with high-grade prostatic intraepithelial neoplasia (HGPIN). Here we report results for serum lycopene, prostate specific antigen (PSA) and insulin-like growth factor (IGF) proteins, histopathological review, and tissue markers for proliferation [minichromosome maintenance protein 2 (MCM-2)] and cell cycle inhibition (p27).
View Article and Find Full Text PDFBackground: Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in fatty acid metabolism that is markedly over-expressed in virtually all prostate cancers (PCa), relative to benign tissue. One of AMACR's primary substrates, phytanic acid, is derived predominately from red meat and dairy product consumption. Epidemiological evidence suggests links between dairy/red meat intake, as well as phytanic acid levels, and elevated PCa risk.
View Article and Find Full Text PDFImportance: Soy consumption has been suggested to reduce risk or recurrence of prostate cancer, but this has not been tested in a randomized trial with prostate cancer as the end point.
Objective: To determine whether daily consumption of a soy protein isolate supplement for 2 years reduces the rate of biochemical recurrence of prostate cancer after radical prostatectomy or delays such recurrence.
Design, Setting, And Participants: Randomized, double-blind trial conducted from July 1997 to May 2010 at 7 US centers comparing daily consumption of a soy protein supplement vs placebo in 177 men at high risk of recurrence after radical prostatectomy for prostate cancer.
Purpose: Sensory trigeminal nerve growth cones innervate the cornea in a highly coordinated fashion. The purpose of this study was to determine if extracellular matrix glycosaminoglycans (ECM-GAGs), including keratan sulfate (KS), dermatan sulfate (DS), and chondroitin sulfate A (CSA) and C (CSC), polymerized in developing eyefronts, may provide guidance cues to nerves during cornea innervation.
Methods: Immunostaining using antineuron-specific-β-tubulin and monoclonal antibodies for KS, DS, and CSA/C was performed on eyefronts from embryonic day (E) 9 to E14 and staining visualized by confocal microscopy.
Previous investigations have linked decreased nuclear expression of the cell cycle inhibitor p27 with poor outcome in prostate cancer. However, these reports are inconsistent regarding the magnitude of that association and its independence from other predictors. Moreover, cytoplasmic translocation of p27 has been proposed as a negative prognostic sign.
View Article and Find Full Text PDFBackground: Molecular markers identifying alterations in proliferation and apoptotic pathways could be particularly important in characterizing high-risk normal or pre-neoplastic tissue. We evaluated the following markers: Ki67, Minichromosome Maintenance Protein-2 (Mcm-2), activated caspase-3 (a-casp3) and Bcl-2 to determine if they showed differential expression across progressive degrees of intraepithelial neoplasia and cancer in the prostate. To identify field effects, we also evaluated whether high-risk expression patterns in normal tissue were more common in prostates containing cancer compared to those without cancer (supernormal), and in histologically normal glands adjacent to a cancer focus as opposed to equivalent glands that were more distant.
View Article and Find Full Text PDFBackground: Alpha-methylacyl-CoA racemase (AMACR) is strongly expressed in prostate cancer with variable expression in high-grade prostatic intraepithelial neoplasia (HGPIN) and low expression in normal prostate. We examined whether AMACR expression in HGPIN and normal tissue was associated with subsequent diagnosis of cancer or proximity to a cancer focus.
Methods: Needle core biopsies from 45 patients with isolated HGPIN, 12 radical prostatectomy (RP) specimens with prostatic carcinoma and 6 cystoprostatectomies without prostatic carcinoma were immunostained for AMACR.